Inhibition of the uncoating of bovine enterovirus by short chain fatty acids

Ismail-Cassim, N.; Chezzi, Carlo; Newman, J. F. E.

doi:10.1099/0022-1317-71-10-2283

Cited by 13 publications

(8 citation statements)

References 16 publications

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“…LNnT produced larger amounts of gas, total SCFA, acetate and butyrate than did other substrates (polydextrose/galacto-oligosaccharides, short-chain fructo-oligosaccharides or iHMO) ( 16 ) . Previous studies have shown that SCFA inhibit the replication of bovine enterovirus, but were almost ineffective against other viruses such as poliovirus type 1, coxsackievirus B5, encephalomyocarditis virus and human rhinovirus 1B ( 47 ) . Ismail-Cassim et al ( 47 ) showed that lauric acid could bind to bovine enterovirus.…”

Section: Discussionmentioning

confidence: 99%

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

et al. 2013

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Human milk (HM) is rich in oligosaccharides (HMO) that exert prebiotic and anti-infective activities. HM feeding reduces the incidence of rotavirus (RV) infection in infants. Herein, the anti-RV activity of oligosaccharides was tested in an established in vitro system for assessing cellular binding and viral infectivity/replication, and also tested in a newly developed, acute RV infection, in situ piglet model. For the in vitro work, crude HMO isolated from pooled HM, neutral HMO (lacto-N-neotetraose, LNnT; 2 0 -fucosyllactose) and acidic HMO (aHMO, 3 0 -sialyllactose, 3 0 -SL; 6 0 -sialyllactose, 6 0 -SL) were tested against the porcine OSU strain and human RV Wa strain. The RV Wa strain was not inhibited by any oligosaccharides. However, the RV OSU strain infectivity was dose-dependently inhibited by sialic acid (SA)-containing HMO. 3 0 -SL and 6 0 -SL concordantly inhibited 125 I-radiolabelled RV cellular binding and infectivity/replication. For the in situ study, a midline laparotomy was performed on 21-d-old formula-fed piglets and six 10 cm loops of ileum were isolated in situ. Briefly, 2 mg/ml of LNnT, aHMO mixture (40 % 6 0 -SL/10 % 3 0 -SL/50 % SA) or media with or without the RV OSU strain (1 £ 10 7 focus-forming units)were injected into the loops and maintained for 6 h. The loops treated with HMO treatments þ RV had lower RV replication, as assessed by non-structural protein-4 (NSP4) mRNA expression, than RV-treated loops alone. In conclusion, SA-containing HMO inhibited RV infectivity in vitro; however, both neutral HMO and SA with aHMO decreased NSP4 replication during acute RV infection in situ.Key words: Human milk oligosaccharides: Rotavirus: Piglets: Infection Rotaviruses (RV) are double-stranded RNA viruses of the family Reoviridae, which are the most common viral agents causing viral gastroenteritis and diarrhoea in infants and young children worldwide. Each year, approximately 1·4 billion episodes of RV gastroenteritis (RVGE) occur in children under 5 years of age in developing countries, and half a million children die (1,2) .Vaccination is the main public health intervention to prevent RV infection. Systematic reviews of vaccine effectiveness and vaccination-impact studies in industrialised countries (USA, Europe and Australia) have demonstrated an effectiveness of 85 -100 % associated with decreased hospitalisations for RVGE (3) . Vaccination-impact studies have demonstrated that the burden of RVGE has been reduced significantly since the introduction of RV vaccination (3) . However, efficacy trials in developing countries in Africa and Asia showed that vaccine efficacy was lower than that observed in other countries, typically 40 -70 % (4) . Although the efficacy of RV vaccines correlates closely with the national per capita income (5) , it is unclear why vaccination is less efficacious in developing countries (6) . This reduced vaccine efficacy coupled with the high cost and barriers to a widespread distribution of RV vaccines (7) suggest that other means for preventing RV should...

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Section: Discussionmentioning

confidence: 99%

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

et al. 2013

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“…Known pocket factors are fatty acid (FA) or FA based; poliovirus uses sphingosine (14), coxsackievirus B3 and EV1 both use palmitate (3,11), and bovine enterovirus uses myristate (15). Enterovirus uncoating can be inhibited by pocket factor mimetics like WIN compounds (10,14) and by the pocket factor itself (5). The uncoating of EV, but not poliovirus, can also be blocked by normal albumin (18); since this protein contains FAs (7), we considered the possibility that FAs were responsible for this block.…”

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confidence: 99%

Fatty Acid-Depleted Albumin Induces the Formation of Echovirus A Particles

Ward

Powell

Chaudhry

et al. 2000

J Virol

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Picornavirus infection requires virus uncoating, associated with the production of 135S "A" particles and 80S empty particles from 160S mature virions, to release the RNA genome into the cell cytoplasm. Normal albumin inhibits this process. We now show that when depleted of fatty acids, albumin induces the formation of echovirus A particles.Echoviruses (EVs), members of the Enterovirus genus of the family Picornaviridae, are small positive-strand RNA viruses with icosahedral symmetry which produce a broad spectrum of diseases in humans (8). Productive cell infection requires the uncoating of the virus particle and release of the RNA genome into the cell cytoplasm. The conversion of the 160S mature virions into 135S A and 80S empty particles (reviewed in reference 14) is considered indicative of this process. Poliovirus A particle formation can be induced by soluble poliovirus receptor (6, 20), whereas soluble decay-accelerating factor, a receptor for a number of enteroviruses including EV12 (17), does not induce EV A particles (12). Moreover, conversion of poliovirus to A particles is rapid compared with the conversion of EV (12). Both uncoating and the thermal stability of virions are thought to be regulated by the presence of "pocket factors" in the hydrophobic pocket at the base of the canyon floor. Known pocket factors are fatty acid (FA) or FA based; poliovirus uses sphingosine (14), coxsackievirus B3 and EV1 both use palmitate (3, 11), and bovine enterovirus uses myristate (15). Enterovirus uncoating can be inhibited by pocket factor mimetics like WIN compounds (10,14) and by the pocket factor itself (5). The uncoating of EV, but not poliovirus, can also be blocked by normal albumin (18); since this protein contains FAs (7), we considered the possibility that FAs were responsible for this block. However, FA-depleted albumin also blocks EV infection (18). We have now investigated the block on EV infection caused by FA-depleted albumin by using wildtype (WT) EV12 and three thermolabile rhodanine-resistant EV12 mutants (1,2,8).Normal bovine serum albumin (A-7638; Sigma) and FAdepleted albumin (A-0281; Sigma) were solubilized in serumfree Dulbecco modified Eagle medium (DMEM) (final pH 7.4). EV12 and the rhodanine-resistant mutants numbered 9, 17, and 20 were incubated for 1 h at 37°C with normal or FA-depleted albumin (2%, wt/vol), or rhodanine (200 g/ml). Virus was then diluted in serum-free DMEM and adsorbed to 24-well plates of rhabdomyosarcoma (RD) cells at 95% confluency for 30 min. Cells were incubated in serum-free DMEM, and at 7 h postinfection, cells were assayed for infected cells by using an immunofocal assay (18). Preincubation of WT EV12 or mutants 17 or 20 with normal albumin and rhodanine did not affect infectivity, whereas infection by mutant 9 was enhanced by 180% (Fig. 1). In contrast, infectivity of all the viruses was reduced after preincubation with FA-depleted albumin; WT EV12 was decreased by 50%, and infectivity of the more thermolabile rhodanine mutants (8) was reduced by 70% (mutant ...

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“…The low-affinity closed conformation of these viruses predominates below physiological temperature and is stabilized at physiological temperature by molecules that bind the hydrophobic pocket in capsid protein VP1. Pocket factor, modeled as palmitate in the coxsackievirus structure 1COV (Muckelbauer et al, 1995) and lipid-like molecules present in other enteroviruses and rhinoviruses have lengths ranging from eight to eighteen carbons (Ismail-Cassim et al, 1990; Liu et al, 2015; Plevka et al, 2012; Smyth and Martin, 2002). Pocket-binding antiviral drugs, such as WIN compounds, interfere with the capsid conformational dynamics, stabilizing the capsids to the extent that genome uncoating is inhibited (Lewis et al, 1998; Liu et al, 2015; Reisdorph et al, 2003; Schmidtke et al, 2005; Tsang et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

MOPS and coxsackievirus B3 stability

2017

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Study of coxsackievirus B3 strain 28 (CVB3/28) stability using MOPS to improve buffering in the experimental medium revealed that MOPS (3-morpholinopropane-1-sulfonic acid) increased CVB3 stability and the effect was concentration dependent. Over the pH range 7.0 to 7.5, virus stability was affected by both pH and MOPS concentration. Computer-simulated molecular docking showed that MOPS can occupy the hydrophobic pocket in capsid protein VP1 where the sulfonic acid head group can form ionic and hydrogen bonds with Arg95 and Asn211 near the pocket opening. The effects of MOPS and hydrogen ion concentrations on the rate of virus decay were modeled by including corresponding parameters in a recent kinetic model. These results indicate that MOPS can directly associate with CVB3 and stabilize the virus, possibly by altering capsid conformational dynamics.

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Inhibition of the uncoating of bovine enterovirus by short chain fatty acids

Cited by 13 publications

References 16 publications

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

Fatty Acid-Depleted Albumin Induces the Formation of Echovirus A Particles

MOPS and coxsackievirus B3 stability

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